WO2009121031A4 - Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases - Google Patents

Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases Download PDF

Info

Publication number
WO2009121031A4
WO2009121031A4 PCT/US2009/038685 US2009038685W WO2009121031A4 WO 2009121031 A4 WO2009121031 A4 WO 2009121031A4 US 2009038685 W US2009038685 W US 2009038685W WO 2009121031 A4 WO2009121031 A4 WO 2009121031A4
Authority
WO
WIPO (PCT)
Prior art keywords
hsa
mir
vascular
related disease
individual
Prior art date
Application number
PCT/US2009/038685
Other languages
French (fr)
Other versions
WO2009121031A1 (en
Inventor
David Marshall Mann
Original Assignee
Vascular Biosciences, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vascular Biosciences, Inc. filed Critical Vascular Biosciences, Inc.
Priority to EP09726302A priority Critical patent/EP2279267A4/en
Priority to EP15182408.3A priority patent/EP2977468B1/en
Priority to US12/934,950 priority patent/US8741861B2/en
Publication of WO2009121031A1 publication Critical patent/WO2009121031A1/en
Publication of WO2009121031A4 publication Critical patent/WO2009121031A4/en
Priority to US14/294,329 priority patent/US9499816B2/en
Priority to US16/908,540 priority patent/US20210010082A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2006—IL-1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/112—Disease subtyping, staging or classification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/136—Screening for pharmacological compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/24—Metalloendopeptidases (3.4.24)
    • C12Y304/24007—Interstitial collagenase (3.4.24.7), i.e. matrix metalloprotease 1 or MMP1

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • General Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The present invention discloses multiple treatment regimens for vascular-related diseases and disorders. The present invention provides for methods of treating vascular-related disorders based on gene expression studies from samples collected from individuals having symptoms of vascular-related disorders. Additionally, methods are disclosed involving diagnostic techniques to focus treatment regimens. Finally, methods of treating vascular-related disorder involving targeting microRNAs are also disclosed.

Claims

AMENDED CLAIMS received by the International Bureau on 26 September 2009 (26.09.2009)
1. A method of diagnosing an individual suffering from a vascular-related disease comprising the steps of: a) obtaining a biopsy sample from an artery of the individual; b) analyzing gene expression levels of the biopsy sample from the artery of the individual and a non-diseased control; c) comparing the gene expression levels between the biopsy sample from the artery of the individual and the non-diseased control; d) identifying at least one gene from step c) that is upregulated or downregulated in the biopsy sample based on the non-diseased control; e) obtaining gene products from the genes identified in step c) ; and f) selecting pharmaceutical agents which are known inhibitors of the gene products from the at least one upregulated gene or known promoters of the gene products from the at least one downregulated gene, wherein the pharmaceutical agents selected are administered to the individual suffering from the vascular-related disease.
2. The method of claim 1, wherein the vascular-related disease is pulmonary arterial hypertension.
3. The method of claim 1, wherein the biopsy sample is extracted using an endoarterial catheter.
4. The method of claim 1, wherein the gene expression levels are analyzed by extracting RNA from the biopsy sample.
5. The method of claim 4, wherein the RNA is converted to cDNA and the cDNA is compared in step c).
6. The method of claim 1, wherein step b) is accomplished using a microarray.
7. The method of claim 1, wherein the vascular-related disease is identified as early, early-mid, late-mid or late stage.
8. The method of claim 1, wherein the analyzing gene expression levels are for genes previously associated with the vascular-related disease.
9. The method of claim 1, wherein the analyzing gene expression levels are for genes not previously associated with the vascular-related disease.
10. A method of diagnosing a vascular-related disease in an individual comprising the steps of: a) identifying at least one gene that is upregulated or downregulated in the vascular-related disease comprising the steps of:
1) obtaining a biopsy sample from the individual's pulmonary artery during progression of the vascular-related disease;
2) obtaining a pulmonary artery sample from a non-diseased control;
3) extracting RNA from the samples in steps 1) and 2) ;
4) obtaining gene products from the RNA extracted in step 3); and 5) comparing gene expression levels from, the biopsy sample with the non-diseased control, and b) associating the genes upregulated in the biopsy sample with an inhibitor of the gene products for administration to the individual and genes downregulated in the biopsy sample with a promoter of the gene products for administration to the individual.
11. The method of claim 10, wherein the vascular-related disease is pulmonary arterial hypertension.
12. The method of claim 10, wherein the biopsy sample is extracted using an endoarterial catheter.
13. A method of identifying microRNA dysregulated in an individual having a vascular-related disease comprising the steps of: a) obtaining a biopsy sample from the individual's pulmonary artery during progression of the vascular-related disease; b) obtaining a pulmonary artery sample from, a non- diseased control; c) extracting RNA from the samples in steps a) and b); d) converting the RNA to cDNA; e) comparing levels of microRNA expression from the biopsy sample with the non-diseased control; and f) identifying the microRNA dysregulated in the vascular-related disease relative to baseline.
14. The method of claim 13/ wherein the vascular-related disease is pulmonary arterial hypertension.
15. The method of claim 13, wherein the microRNA is measured according to stages of progression of the vascular-related disease.
16. A use of targeting microRNAs in the preparation of a medicament for the treatment of a vascular-related disease comprising the following steps: a) assessing a stage of the vascular-related disease in the individual; b) identifying whether microRNAs are upregulated or downregulated; c) selecting the microRNAs to target based on the stage of the vascular-related disease and whether the aicroRNAs are upregulated or downregulated; and d) administering an agent known to inhibit an upregulated microRNA or an agent known to promote a downregulated microRNA to the individual, wherein the stage of the vascular-related disease is based on flow rates and blood pressure within an artery of the individual.
17. The use of claim 16, wherein the vascular-related disease is pulmonary arterial hypertension.
18. The use of claim 16, wherein the microRNAs to target are any microRNAs listed in Tables 12-17.
19. The use of claim 16, wherein the stage of the vascular-related disease is one of high flow and high pressure within the artery of the individual.
20. The use of claim 19, wherein the upregulated microRNAs to inhibit under the stage of high flow and high pressure comprise at least one member selected from the group consisting of hsa-miR-520g, hsa-miR-331-5p, hsa-miR-410, hsa-let-7d, hsa-miR-187, hsa-miR-16-2, hsa-miR-130a, hsa- miR-548n, hsa-miR-127-5p, solexa-2580-353, HS_206, hsa-miR- 663, solexa-7534-111, hsa-let-7g, HS_157, hsa-miR-610, HS_251.1, hsa-miR-519e, hsa-miR-1237, hsa-miR-1185, HS_1S1.1, HS_135, solexa-3126-285, hsa-miR-30a, hsa-miR- 192, hsa-miR-568, hsa-miR-1203, hsa-miR-28-Sp, HS_262.1, HS_170, hsa-miR-1273, hsa-miR-602, hsa-miR-374a and hsa- miR-29a.
21. The use of claim 16, wherein the stage of the vascular-related disease is one of high flow and low pressure within the artery of the individual.
22. The use of claim 21, wherein the upregulated microRNAs to inhibit under the stage of high flow and low pressure comprise at least one member selected from the group consisting of HS_70, hsa-let-7d, hsa-miR-187, solexa-2580- 353, HS_157, solexa-7534-111, hsa-miR-130a, HS_135, hsa- miR-192, hsa-miR-154, hsa-miR-151:9.1, hsa-miR-1203, hsa- miR-525-3p and HS_199.
23. The use of claim 19, wherein the downregulated microRNAs to promote under the stage of high flow and high pressure comprise at least one member selected from the group consisting of solexa-603-1846, hsa-miR-586, hsa-miR- 1201, hsa-miR-33a, HS_56, h6a-miR-520d:9.1, hsa-miR-521, hsa-miR-519a, HS_134, HS_169, HS_221, hsa-miR-496, hsa-miR- 935, hsa-miR-542-5p, solexa-5620-151, hsa-miR-99a, hsa-miR- 212, hsa-let-7f-2, hsa-miR-494, hsa-miR-1321, hsa-miR-219- 2-3p, hsa-miR-95, hsa-miR-128b:9.1, hsa-miR-33a, hsa-miR- 495, hsa-miR-1229, hsa-miR-1205, hsa-miR-524-3p, HS_150, hsa-miR-135a, hsa-miR-483-5p, hsa-miR-124a:9.1, hsa-miR- 29b-1, hsa-miR-548c-5p, hsa-miR-551a, hsa-miR-377 and hsa- miR-1304.
24. The use of claim 21, wherein the downregulated microRNAs to promote under the stage of high flow and low pressure comprise at least one member selected from the group consisting of HS_104, hsa-miR-548a-5p, hsa-miR-556- 5p, HS_169, HS_140, hsa-miR-542-5p, HS_134, hsa-miR-212, hsa-miR-363, HS_59, hsa-miR-586, hsa-miR-494, hsa-miR-1205, hsa-let-7f-2, hsa-miR-483-5p, HS_150, hsa-miR-1229, HS_156, hsa-miR-619, hsa-miR-10b and h3a-miR-371-5p.
25. A method of diagnosing an individual having a vascular-related disease according to claim 1, further wherein the individual is categorized based on progression of the vascular-related disease.
26. The method of claim 25, wherein the progression of the vascular-related disease is selected from the group consisting of early stage, mid stage and late stage.
27. The method of claim 26, wherein the pharmaceutical agent to treat the early stage progression of the vascular- related disease is at least one member selected from the group consisting of the drugs listed in Table 3.
28. The method of claim 26, wherein the pharmaceutical agent to treat the mid stage progression of the vascular- related disease is at least one member selected from the group consisting of the drugs listed in Tables 4 and 5.
29. The method of claim 26, wherein the pharmaceutical agent to treat the late stage progression of the vascular- related disease is at least one member selected from the group consisting of the drugs listed in Table 6.
30. The method of claim 1, wherein the diagnosing of the individual may be modified over the course σf disease progression.
31. A method of diagnosing a vascular-related disease comprising creating a custom microarray capable of measuring gene expression levels specific to genes under control by a known drug to determine drug activity.
32. The method of claim 31, wherein the gene expression levels are determined from a member selected from the group consisting of kit, abll, pdgfra and pdgfrb and the known drug is imatinib.
33. A use of at least one drug selected from Tables 2, 3 and 4 in the preparation of a medicament for the treatment of a vascular-related disease.
34. The use of claim 33, wherein the vascular-related disease is pulmonary hypertension.
35. The method of claim 1, wherein the artery is a pulmonary artery.
PCT/US2009/038685 2008-03-27 2009-03-27 Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases WO2009121031A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP09726302A EP2279267A4 (en) 2008-03-27 2009-03-27 Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases
EP15182408.3A EP2977468B1 (en) 2008-03-27 2009-03-27 Methods of novel therapeutic candidate identification through gene expression analysis in pulmonary arterial hypertension
US12/934,950 US8741861B2 (en) 2008-03-27 2009-03-27 Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases
US14/294,329 US9499816B2 (en) 2008-03-27 2014-06-03 Methods of novel therapeutic candidate identification through gene expression analysis in vascular related diseases
US16/908,540 US20210010082A1 (en) 2008-03-27 2020-06-22 Methods of Novel Therapeutic Candidate Identification Through Gene Expression Analysis in Vascular-Related Diseases

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4006508P 2008-03-27 2008-03-27
US61/040,065 2008-03-27

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/934,950 A-371-Of-International US8741861B2 (en) 2008-03-27 2009-03-27 Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases
US14/294,329 Division US9499816B2 (en) 2008-03-27 2014-06-03 Methods of novel therapeutic candidate identification through gene expression analysis in vascular related diseases

Publications (2)

Publication Number Publication Date
WO2009121031A1 WO2009121031A1 (en) 2009-10-01
WO2009121031A4 true WO2009121031A4 (en) 2009-11-19

Family

ID=41114352

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/038685 WO2009121031A1 (en) 2008-03-27 2009-03-27 Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases

Country Status (3)

Country Link
US (4) US8741861B2 (en)
EP (2) EP2279267A4 (en)
WO (1) WO2009121031A1 (en)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ556673A (en) 2005-02-03 2010-03-26 Gen Hospital Corp Method for treating gefitinib and/or erlotinib resistant cancer with an EGFR inhibitor
KR101354828B1 (en) 2005-11-04 2014-02-18 와이어쓰 엘엘씨 Antineoplastic combinations with mtor inhibitor, herceptin, and/or hki-272
WO2009018493A1 (en) 2007-07-31 2009-02-05 The Board Of Regents Of The University Of Texas System A micro-rna family that modulates fibrosis and uses thereof
US8022216B2 (en) 2007-10-17 2011-09-20 Wyeth Llc Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof
JP5654352B2 (en) 2007-11-09 2015-01-14 ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム Regulation of cardiomyocyte survival and cardiac repair by miR-15 family of microRNAs
EP3730139B1 (en) 2008-06-17 2023-08-16 Wyeth LLC Antineoplastic combinations containing hki-272 and vinorelbine
KR101434009B1 (en) 2008-08-04 2014-08-25 와이어쓰 엘엘씨 Antineoplastic combinations of 4-anilino-3-cyanoquinolines and capecitabine
JP5992325B2 (en) 2009-04-06 2016-09-14 ワイス・エルエルシー Treatment plans utilizing neratinib for breast cancer
EP2476758A4 (en) * 2009-09-07 2013-04-03 Yoshiki Murakami Method for prediction of therapeutic effect on chronic hepatitis c
WO2011058367A2 (en) 2009-11-13 2011-05-19 Astrazeneca Ab Diagnostic test for predicting responsiveness to treatment with poly(adp-ribose) polymerase (parp) inhibitor
EP2385120A1 (en) * 2010-05-04 2011-11-09 Justus-Liebig- Universitat Giessen Use of anti-miRNA antisense oligonucleotides for the treatment of pulmonary hypertension
CN103582480B (en) * 2011-02-09 2016-03-16 医药公司 The method for the treatment of pulmonary hypertension
KR20140037868A (en) 2011-05-09 2014-03-27 더 유니버시티 코트 오브 더 유니버시티 오브 글래스고우 Methods of modulating micrornas in the treatment of pulmonary arterial hypertension
AU2013248972A1 (en) 2012-04-20 2014-11-13 Adhaere Pharmaceuticals, Inc. Compounds and methods for regulating integrins
US9163235B2 (en) 2012-06-21 2015-10-20 MiRagen Therapeutics, Inc. Inhibitors of the miR-15 family of micro-RNAs
US9603890B2 (en) * 2012-12-03 2017-03-28 Vascular Biosciences Methods for increasing the selective efficacy of gene therapy using CAR peptide and heparan-sulfate mediated macropinocytosis
EP2968396B1 (en) 2013-03-15 2018-12-19 Miragen Therapeutics, Inc. Locked nucleic acid inhibitor of mir-145 and uses thereof
WO2015171641A1 (en) * 2014-05-05 2015-11-12 Brigham And Women's Hospital, Inc. Coordinate control of pathogenic signaling by the mir-130/301 family in pulmonary hypertension and fibroproliferative diseases
CA2889826A1 (en) 2014-06-20 2015-12-20 Emmanuel E. Egom Methods of treating pulmonary hypertention by administration of natriuretic peptide receptor c signaling pathway activators
CN104789683B (en) * 2015-05-01 2018-08-28 北京博奥医学检验所有限公司 Biomarker and application thereof for diagnosis and treatment metastasis of cancer
CN114272389B (en) 2016-03-02 2023-04-18 卫材研究发展管理有限公司 Eribulin-based antibody-drug conjugates and methods of use
KR102434879B1 (en) * 2016-05-26 2022-08-22 유니버시티 오브 피츠버그 - 오브 더 커먼웰쓰 시스템 오브 하이어 에듀케이션 Composition and method for treating pulmonary vascular disease
WO2018073687A1 (en) * 2016-10-20 2018-04-26 Pfizer Inc. Anti-proliferative agents for treating pah
MX2019007389A (en) 2016-12-20 2019-08-16 Lts Lohmann Therapie Systeme Ag Transdermal therapeutic system containing asenapine and polysiloxane or polyisobutylene.
US20180193283A1 (en) 2016-12-20 2018-07-12 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system containing asenapine
CN110799204A (en) * 2017-05-19 2020-02-14 小利兰·斯坦福大学理事会 Enzastaurin and fragile histidine triad (FHIT) enhancer for treating pulmonary hypertension
JP2020525545A (en) 2017-06-26 2020-08-27 エルテーエス ローマン テラピー−ジステーメ アーゲー Transdermal therapeutic system containing asenapine and silicone-acrylic hybrid polymer
CN109776788B (en) * 2017-11-14 2021-07-30 博瑞生物医药（苏州）股份有限公司 Folate receptor targeted multi-arm conjugates
CA3101420A1 (en) 2018-06-20 2019-12-26 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system containing asenapine
CN116726037A (en) * 2023-06-25 2023-09-12 湖南师范大学 Application of fludarabine in preparation of medicines for treating pulmonary hypertension

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5287857A (en) * 1992-06-22 1994-02-22 David Mann Apparatus and method for obtaining an arterial biopsy
US20050037946A1 (en) * 2003-01-13 2005-02-17 Millennium Pharmaceuticals, Inc. Methods and compositions for treating cardiovascular disease using 1722, 10280, 59917, 85553, 10653, 9235, 21668, 17794, 2210, 6169, 10102, 21061, 17662, 1468, 12282, 6350, 9035, 1820, 23652, 7301, 8925, 8701, 3533, 9462, 9123, 12788, 17729, 65552, 1261, 21476, 33770, 9380, 2569654, 33556, 53656, 44143, 32612, 10671, 261, 44570, 41922, 2552, 2417, 19319, 43969, 8921, 8993, 955, 32345, 966, 1920, 17318, 1510, 14180, 26005, 554, 16408, 42028, 112091, 13886, 13942, 1673, 54946 or 2419
US20050037366A1 (en) * 2003-08-14 2005-02-17 Joseph Gut Individual drug safety
US20060019272A1 (en) * 2004-05-03 2006-01-26 The Regents Of The University Of Colorado Diagnosis of disease and monitoring of therapy using gene expression analysis of peripheral blood cells
ES2503765T3 (en) * 2004-11-12 2014-10-07 Asuragen, Inc. Procedures and compositions involving miRNA and miRNA inhibitor molecules
US20060185027A1 (en) * 2004-12-23 2006-08-17 David Bartel Systems and methods for identifying miRNA targets and for altering miRNA and target expression
US8795668B2 (en) * 2005-12-23 2014-08-05 The Regents Of The University Of Michigan Methods for treating pulmonary fibrosis
CN101675165A (en) * 2006-12-08 2010-03-17 奥斯瑞根公司 The function of LET-7 Microrna and target

Also Published As

Publication number Publication date
WO2009121031A1 (en) 2009-10-01
US9499816B2 (en) 2016-11-22
EP2977468A2 (en) 2016-01-27
US20170145505A1 (en) 2017-05-25
EP2977468B1 (en) 2019-06-19
EP2279267A1 (en) 2011-02-02
US20210010082A1 (en) 2021-01-14
EP2279267A4 (en) 2012-01-18
US20110091421A1 (en) 2011-04-21
US20140323335A1 (en) 2014-10-30
EP2977468A3 (en) 2016-04-27
US8741861B2 (en) 2014-06-03

Similar Documents

Publication Publication Date Title
WO2009121031A4 (en) Methods of novel therapeutic candidate identification through gene expression analysis in vascular-related diseases
Mura et al. Gene expression profiling in the lungs of patients with pulmonary hypertension associated with pulmonary fibrosis
Zhang et al. Circulating CCL20: A potential biomarker for active vitiligo together with the number of Th1/17 cells
JP2011510650A5 (en)
WO2011117366A3 (en) Genes and genes combinations predictive of early response or non response of subjects suffering from inflammatory disease to cytokine targeting drugs (cytd)
CN107326071B (en) Application of PLPP4 as non-small cell lung cancer diagnosis, treatment and prognosis target
KR20130069633A (en) Means and methods for determining risk of cardiovascular disease
US10233500B2 (en) MicroRNAs characterizing rosacea and the uses thereof
Zeng et al. Insulin treatment affects leukocyte telomere length in patients with type 2 diabetes: 6-year longitudinal study
JP6800470B2 (en) Periodontitis test kit and test method using miRNA as a marker
CN105349641B (en) Acute myocardial infarction AMI related gene SERPINB13 and its application
Liang et al. A method establishment and comparison of in vivo lung cancer model development platforms for evaluation of tumour metabolism and pharmaceutical efficacy
JP2014132863A (en) Neurodegenerative disease biomarker
WO2012094366A1 (en) Circulating mirnas as biomarkers for coronary artery disease
Wang et al. The expression research of miR-210 in the elderly patients with COPD combined with ischemic stroke.
RU2481058C1 (en) Predicting risk of ischemic stroke in patients with ischemic heart disease and persistent atrial fibrillation
Hofbauer et al. Arterial hypertension enhances neutrophil extracellular trap formation via an angiotensin-II-dependent pathway
JP6281831B2 (en) Regulators of neurodegenerative diseases
Ebrahim et al. Vitiligo: A comprehensive review
CN110241207A (en) A kind of unstable angina biomarker and its application and kit
Meijin et al. A3081 VDR agonist prevents diabetic endothelial dysfunction through inhibition of prolyl isomerase-1 mediated mitochondrial oxidative stress and inflammation
JP2014128249A (en) USE OF miRNA OR TARGET GENE THEREOF IN INSPECTION AND THERAPY OF NEURODEGENERATIVE DISEASE
RU2693469C1 (en) Method for prediction of men's risk of essential hypertension associated with obesity
WO2007102402A1 (en) Method of diagnosing chronic fatigue syndrome
Huber Splenic Control of Cardiovascular Homeostasis: the role of the spleen in the pathogenesis of cardiovascular disease

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09726302

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2009726302

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 12934950

Country of ref document: US